IRON DEFICIENCY ANEMIA : AN OVERVIEW

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1 IRON DEFICIENCY ANEMIA : AN OVERVIEW Ketut Suega Hematology-Medical Oncology Division Internal department, Udayana Medical School/Sanglah Hospital Denpasar Bali

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9 IRON INDICATORS Normal range Iron deficiency anemia Anemia of chronic disease Serum iron µmol/l Low Low Ferritin, pmol/l low a Normal or raised Transferring, g/l High Low Transferring, saturation, % Total iron binding capacity, µmol/l Red cell morphology Low Normal High Low or normal MCV, 80-95fl MCH concentration, ghb/100ml Microcytic, hypochromic b Normocytic or microcytic, normochromic

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12 TREATMENT Successful overall management of the patient with iron deficiency anemia requires an attempt to identify and treat the underlying cause(s) of the iron deficiency (eg, blood loss from a tumor, varicosity, or other bleeding lesion; iron malabsorption) and the right uses of iron preparations for the treatment of functional iron deficiency.

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14 IRON PREPARATIONS ORAL INTRAVENOUS

15 Elemental iron content of iron salts Iron salt Ferrous sulfate (FeSO, 7H2O) 300 mg Ferrous sulfate dried 200 mg Ferrous fumarate 200 mg Ferrous gluconate 300 mg Ferrous glycine sulfate 225 mg Ferrous succinate 100 mg Ferrous calcium citrate complex/cap Ferrous aminoate (probiotic cap) Ferric amonium citrate 100 mg Elemental iron 60 mg 65 mg 65 mg 35 mg 40 mg 35 mg 250 mg Fe +85 Ca 60 mg 20 mg Bichille et.al.,apicon 2008

16 CHOICE OF PREPARATION The recommended oral daily dose of 150 to 200 mg/day of elemental iron. As an example, a single 325 mg ferrous sulfate tablet taken orally three times daily between meals provides an oral dose of 195 mg of elemental iron per day. There is no evidence that one of the above iron preparations is more effective than another for this purpose. Schrier and Auerbach, Uptodate 2014

17 SIDE EFFECTS Up to 50% of patients complain of nausea, constipation, diarrhea, epigastric distress and/or vomiting after taking various oral iron preparations. However, with the advent of parenteral iron formulations with more favorable toxicity profiles, the early use of intravenous iron should be considered in those intolerant to the use of oral iron preparations Cancelo-Hidago et.al., Curr Med Res Opin,2013

18 Oral iron therapy There are numerous conditions, however, for which oral iron is either poorly tolerated. GI side effects may result in poor adherence to therapy. Malabsorptive states associated with an inability to absorb iron optimally. Oral iron may take 6 months in order to replete iron stores. In IBD the use of oral iron associated with worsening the disease. In conditions such as heavy blood loss, absorption of oral iron, even in maximal doses, may be unable to keep up with blood loss. Dialysis patients, especially those being treated with ESAs, are unable to utilize iron orally. Pasricha et.al.,blood 2013 Gasche et.al.,inflam Bowel Dis 2007 Auerbach et.al., Transfusion 2008 Bergmann et.al.,am J Hematol 2013

19 Parenteral iron. However there are numerous settings in which the use of intravenous iron preparations may be preferable. The early switch to intravenous iron should be considered in those intolerant to the use of oral iron preparations. The maximum amount of elemental iron absorbed with an oral is 25 mg/day, whereas, up to 1000 mg of elemental iron can be administered with IV iron. Published evidence supports the IV iron as an early option for those withibd. NCCN state that IV iron is the preferred when iron is indicated, and K/DOQI indicate its use for iron replacement in dialysis patients. IV iron is required when the amount of iron lost exceeds the capacity of the GI tract to absorb oral iron preparations. For gastric bypass surgery and/or subtotal gastric resection, makes IV iron an especially good choice. Gasche, Gut 2004 Werner et.al., Duetsch Med W, 1977

20 Intravenous iron preparations Drug Trade name Max. dose mg elemental Iron dextran (HMW) TDI possibl Premedicati on Tes dose Elemental (mg/ ml) Preservati ve Dexfernum 100 Yes TDI Only Required 50 None Iron dextran ( LMW) INFeD 100 Yes TDI Only Required 50 None Feric gluconate Ferifact 125 No No Recomm. if allergies 12.5 Benzyl alcohol Iron sucrose Venofer 200 to 300 No No Reccom. if allergies 20 None Ferumoxytol Feraheme 510 No No No 30 None Iron isomaltoside Feric carboxymatose Monofer (Not in US) Ferinject (not in US) 20 mg/kg Yes No No 100 None 20 mg/kg (max1000mg) No No No 50 None The USE of high molecular weight iron dextran preparations, rather than low molecular weight iron dextran preparations, is not recommended, due to a higher inodence of adverse reactions Available in certain European countries. Common European trade name shown.

21 SIMPLE SCHEME FOR THE ESTIMATION OF TOTAL IRON NEED Degree of Iron Deficiency Hemoglobin Level, g/dl Dose for Body Weight <70 kg, mg No anemia Normal Moderate (women) (men) Severe Critical < Dose for Body Weight 70 kg, mg Evstatiev et al.,2011

22 EXPECTED RESPONSE If pagophagia or RLS is present, it disappears soon and the patient will note an improved feeling of well-being within the first few days In patients with moderate to severe anemia, a modest reticulocytosis will be seen, maximal in approximately 7 to 10 days. Hb will rise approximately 2 g/dl over 3 weeks, should be halved in 1 month, return to normal by 6-8 weeks. Following iron repletion, a rapid correction of papillae (weeks to months) is observed. Santiago,Scientific World J,2012 Schrier and Auerbach, Uptodate 2014

23 Oral Iron preparations Desirable characteristics Should have 150 mg elemental iron (at least 100 mg) Readily released in acidic and neutral ph Salt should be readily absorbable (Ferrous form) Infrequent side effects Should not have several therapeutic agents Small cost Maximum iron absorption in upper part of the duodenum Bichille et.al.,apicon 2008

24 IDEAL PARENTERAL IRON PREP. DELIVERING SUFFICIENT IRON TO CORRECT RAPIDLY MINIMAL POTENTIAL SIDE EFFECTS LOW CATALYTIC/LABILE IRON RELEASE (CONTROLLED RELEASE) NEGLIGIBLE IMMUNOGENICITY WIDE DOSING RANGE TO ALLOW A SINGLE REPLETION DOSE NO REQUIREMENT FOR A TEST DOSE. CONVENIENT AND COST-EFFECTIVE Cancado et.al., RBHH2011; 33 (6) Bandhari, NDT Plus 2011 ;4(S)

25 Blood transfusion Highly restrictive Active bleeding hemodinamically unstable Critical anemia with cardiovascular event Acute myocardial ischemia If all other treatment fail Jimenez et al.,2015

26 SUMMARY IDA WAS STIIL GLOBAL HEALTH PROBLEMS, MOST IDA RESPOND WELL TO ORAL IRON, BUT FOR THOSE NOT DOING SO INTRAVENOUS IRON OFFERS AN EXCELLENT ALTERNARTIVE, EVEN IN CERTAIN CONDITON SUCH AS IBD AND OTHER INFLAMMATIONS INTRAVENOUS IRON WAS THE ONLY OPTION AVAILABLE. IN ADDITION THE UNDERLYING CAUSES HAS TO DEAL PROMPTLY

27 THANK YOU MATUR SUKSMA TERIMAKASIH

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29 There are 2 form iron salts (Ferrous and Ferric irons) and several iron formulations ( carbonyl iron, extended released, parenteral and oral prep.,etc ) The choice of iron preparation depends upon the acuity of illness, as well as the ability of the patient to tolerate oral iron preparations. Tom, Pharmaceut Letter 2008

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31 Oral iron therapy There are numerous conditions, however, for which oral iron is either poorly tolerated. Non-dialysis have reasons for their inability to absorb oral iron (eg, impaired iron transport, concomitant use of calcium-containing salts, H 2 blockers, phosphate binders, generalized malabsorption). Oral iron, does not synergize well with ESAs in anemic cancer patients both on and off chemotherapy. Hepcidin, may result in suboptimal GI absorption of orally iron preps. However 2/3 of the non-responders in this study responded to treatment with intravenous iron. The safety of routine iron in settings where infectious diseases such as malaria are endemic remains uncertain. Pasricha et.al.,blood 2013 Gasche et.al.,inflam Bowel Dis 2007 Auerbach et.al., Transfusion 2008 Bergmann et.al.,am J Hematol 2013

32 INDICATION for PARENTERAL IRON Excessive continuing blood loss - Currently, parenteral iron is most often used in iron deficient patients whose level of continued bleeding exceeds the ability of GI tract to absorb iron. Inflammatory bowel disease Many patients with IBD and iron deficiency have severe intolerance to oral iron preparations, which may also worsen IBD disease activity. Chronic kidney disease IV iron is the current standard in both dialysis and non-dialysis kidney disease patients for multiple reasons Use in cancer patients A large number of prospective studies support the observation that IV iron,synergizes with ESA therapy in anemic cancer patients Gafter-Giulli et.al., Acta Oncol 2013 Gasche,Inflamm Bowel Dis, 2007 Kalantar-Zadeh,Adv Chronic Kidney Dis, 2009

33 Factors influencing the absorption and bioavailability of dietary iron Absorption of heme iron Amourt of heme iron, especially in meat Concent of calcium in the meal (calcium impairs iron absorption) Absorption of nonheme iron Iron status Amount of potentially available nonheme iron Balance between positive and negative factors Positive factors Ascorbic acid Meat of fish (heme iron enhances absorption of nonheme iron) Negative Factors Phytat ( in bran, oats, rye fiber) Pchyphenols (in tea, some vegetables and cereals) Dietary calcium Soy protein Adapted from: Hallberg L, Rossander-Hultan L, Burne M, Nutritional anemias. In: Nestle Workshop Series, vol 30, Fomon Sl, Zoblon S (Eds), Vevey/ Raren Press, New York 1992.p.170.